Analysis Tools
mortality/aging
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• although identified at close to expected ratios at E14 and E16, the ratio of homozygotes declines sharply at E18 (to 4%), with homozygotes rarely surviving past that age
• many embryos display severe degeneration and resorption during early embryogenesis
• among hundreds of homozygotes generated, only one mouse survived for 27 days
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embryo
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• pleiotropic phenotypes resembling Meckel syndrome at E16-E18
• on occasion, abdominal organs are missing
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• at E16
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• neural tube cilia are missing and basal bodies are mislocalized at E12
• cilia-mediated Shh signalling is perturbed in the developing neural tube
• neural tube patterning defects mostly affect ventral cell fates
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• neural tube cilia are missing at E12
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• open rostral neural tube at E16
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• flattening of the embryonic node with only a few cilia-like structures at E8
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• only rare cilia-like structures seen in embryonic node at E8
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growth/size/body
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• at E16
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• gross underdevelopment seen in a single rare survivor at P27
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• often at E16
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cellular
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• only a few or no cilia are seen in perinatal tracheal epithelium
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• embryos display defects in motile and sensory cilia biogenesis
• in culture, ~90% of MEFs derived from E12.5-E13.5 mutant embryos fail to grow cilia upon serum starvation, unlike wild-type MEFs
• mutant MEFs exhibit a basal body but fail to initiate ciliary axoneme biogenesis from the mother centriole; however, cytoplasmic microtubules are observed
• mutant MEFs show lack of or abnormal subdistal appendages in the mother centriole; as a result, microtubules are not anchored and transport vesicles accumulate in the cytoplasm around the mother centriole
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• only rare cilia-like structures seen in embryonic node at E8
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• cilia are absent or abnormal in embryonic liver at E13.5
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• neural tube cilia are missing at E12
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• only a few or no cilia are seen in perinatal kidney tubules
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• kinocilia in the cochlea are frequently absent or misoriented at E18
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• mutant MEFs show lack of or abnormal subdistal appendages in the mother centriole, and display disorganized microtubules and accumulation of transport vesicle-like structures nearby
• in a fraction of MEFs, the mother centriole docks to ciliary vesicles but no transition zone develops
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nervous system
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• kinocilia in the cochlea are frequently absent or misoriented at E18
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• neural tube cilia are missing and basal bodies are mislocalized at E12
• cilia-mediated Shh signalling is perturbed in the developing neural tube
• neural tube patterning defects mostly affect ventral cell fates
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• neural tube cilia are missing at E12
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• open rostral neural tube at E16
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• stereociliary bundles are frequently deformed at E18
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hydrocephaly
(
J:226310
)
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• domed head representing profound hydrocephalus seen in a single rare survivor at P27
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exencephaly
(
J:226310
)
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• often at E16
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• poorly developed inner segments seen in a single rare survivor at P27
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• poorly developed outer segments seen in a single rare survivor at P27
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vision/eye
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• at E16
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• retinal dystrophy seen in a single rare survivor at P27
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• poorly developed inner segments seen in a single rare survivor at P27
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• poorly developed outer segments seen in a single rare survivor at P27
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• severe disruption of the outer nuclear layer seen in a single rare survivor at P27
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anophthalmia
(
J:226310
)
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• at E16
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• little to no light intensity-dependent responses in a and b waves seen in a single rare survivor at P27
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limbs/digits/tail
polydactyly
(
J:226310
)
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• frequently seen at E16
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• pre-axial polydactyly seen in hindlimbs at E16
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respiratory system
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• only a few or no cilia are seen in perinatal tracheal epithelium
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• only a few or no cilia are seen in perinatal tracheal epithelium
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cardiovascular system
dextrocardia
(
J:226310
)
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• often at E16
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hemorrhage
(
J:226310
)
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• at E16
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renal/urinary system
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• only a few or no cilia are seen in perinatal kidney tubules
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hearing/vestibular/ear
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• kinocilia in the cochlea are frequently absent or misoriented at E18
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• stereociliary bundles are frequently deformed at E18
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integument
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• loss of hair on the dorsal surface seen in a single rare survivor at P27
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behavior/neurological
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Meckel syndrome | DOID:0050778 |
OMIM:PS249000 |
J:226310 | |
